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1.
Braz J Microbiol ; 54(4): 2817-2826, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37828396

RESUMEN

This study aimed to compare the efficacy of fosfomycin, colistin, tobramycin and their dual combinations in an experimental sepsis model. After sepsis was established with a Pseudomonas aeruginosa isolate (P1), antibiotic-administered rats were divided into six groups: Fosfomycin, tobramycin, colistin and their dual combinations were administered by the intravenous or intraperitoneal route to the groups. The brain, heart, lung, liver, spleen and kidney tissues of rats were cultured to investigate bacterial translocation caused by P1. Given the antibiotics and their combinations, bacterial colony counts in liver tissues were decreased in colistin alone and colistin plus tobramycin groups compared with control group, but there were no significant differences. In addition, a non-statistical decrease was found in the spleen tissues of rats in the colistin plus tobramycin group. There was a > 2 log10 CFU/ml decrease in the number of bacterial colonies in the kidney tissues of the rats in the fosfomycin group alone, but the decrease was not statistically significant. However, there was an increase in the number of bacterial colonies in the spleen and kidney samples in the group treated with colistin as monotherapy compared to the control group. The number of bacterial colonies in the spleen samples in fosfomycin plus tobramycin groups increased compared to the control group. Bacterial colony numbers in all tissue samples in the fosfomycin plus colistin group were found to be close to those in the control group. Colistin plus tobramycin combinations are effective against P. aeruginosa in experimental sepsis, and clinical success may be achieved. New in vivo studies demonstrating the ability of P. aeruginosa to biofilm formation in tissues other than the lung are warranted in future.


Asunto(s)
Fosfomicina , Infecciones por Pseudomonas , Sepsis , Animales , Ratas , Pseudomonas aeruginosa , Fosfomicina/farmacología , Fosfomicina/uso terapéutico , Colistina/farmacología , Colistina/uso terapéutico , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Tobramicina/farmacología , Tobramicina/uso terapéutico , Sepsis/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana
2.
Int J Mol Sci ; 24(15)2023 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-37569331

RESUMEN

C-Vx is a bioprotective product designed to boost the immune system. This study aimed to determine the antiviral activity of the C-Vx substance against SARS-CoV-2 infection. The effect of C-Vx in K18-hACE2 transgenic mice against the SARS-CoV-2 virus was investigated. For this purpose, ten mice were separated into experimental and control groups. Animals were infected with SARS-CoV-2 prior to the administration of the product to determine whether the product has a therapeutic effect similar to that demonstrated in previous human studies, at a histopathological and molecular level. C-Vx-treated mice survived the challenge, whereas the control mice became ill and/or died. The cytokine-chemokine panel with blood samples taken during the critical days of the disease revealed detailed immune responses. Our findings showed that C-Vx presented 90% protection against the SARS-CoV-2 virus-infected mice. The challenge results and cytokine responses of K18-hACE2 transgenic mice matched previous scientific studies, demonstrating the C-Vx's antiviral efficiency.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , Ratones , Animales , Ratones Transgénicos , Antivirales/farmacología , Antivirales/uso terapéutico , Citocinas , Modelos Animales de Enfermedad
3.
Emerg Microbes Infect ; 11(1): 2698-2710, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36106521

RESUMEN

The modulatory effect of C-Vx, a novel therapeutic agent, on the immune system of COVID-19 patients was investigated. The functions of T and NK cells of COVID-19 patients with different disease severity were evaluated by flow cytometry in response to C-Vx stimulation. The levels of pro- and anti-inflammatory cytokines were detected by multiplex assay in supernatants after cell culture with C-Vx. Bradykinin, IRF3, and IFN-α levels were also measured by ELISA in the presence or absence of C-Vx stimulation. As a result, increased CD107a expression was observed on NK cells in response to C-Vx addition. The proliferation of T cell subsets was increased by C-Vx, decreasing by disease severity. IL-4 and IL-10 levels were elevated while IFN-γ and IL-17 levels were reduced in T cells following C-Vx stimulation. However, the levels of pro-inflammatory IL-1ß, IL-6, IL-8, IFN-γ and GM-CSF were significantly increased upon C-Vx stimulation. IFN-α levels tended to increase after incubation with C-Vx. These findings support an immunomodulatory action of C-Vx on the immune system of patients with a mild and moderate phase of COVID-19.


Asunto(s)
COVID-19 , Humanos , Citocinas , Interferón gamma/metabolismo , Linfocitos T , Células Asesinas Naturales
4.
Future Microbiol ; 17: 1027-1042, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35796076

RESUMEN

Background: The authors aimed to determine the efficacy of frequently used antibiotics, alone or in combination, against biofilms of ventilator-associated pneumonia isolates. Materials & methods: The authors determined the MICs, minimum biofilm inhibitory concentrations and minimum biofilm eradication concentrations of meropenem, ciprofloxacin and colistin as well as their combinations against planktonic forms and biofilms of Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii clinical isolates. Results: Generally, the minimum biofilm inhibitory concentrations and minimum biofilm eradication concentrations of the antibiotics were 1000-fold higher than their MICs, and synergy was provided by different concentrations of meropenem-colistin and meropenem-ciprofloxacin combinations with checkerboard and time-kill curve methods. Conclusion: The combination of meropenem and ciprofloxacin seems to be a good candidate for the treatment of biofilm-associated infections; none of the concentrations obtained as a result of the synergy test were clinically significant.


Asunto(s)
Acinetobacter baumannii , Neumonía Asociada al Ventilador , Antibacterianos/farmacología , Biopelículas , Ciprofloxacina/farmacología , Colistina/farmacología , Sinergismo Farmacológico , Humanos , Meropenem/farmacología , Pruebas de Sensibilidad Microbiana , Neumonía Asociada al Ventilador/tratamiento farmacológico
5.
Acta Microbiol Immunol Hung ; 69(3): 215-219, 2022 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-35895557

RESUMEN

Treatment of infections caused by OXA-48 carbapenemase producing multidrug-resistant isolates often necessitates combination therapy. In vitro effect of different antibiotic combinations against multidrug-resistant (MDR) Klebsiella pneumoniae isolates were evaluated in this study.Meropenem-tobramycin (MER+TOB), meropenem-ciprofloxacin (MER+CIP), colistin-meropenem (COL+MER), colistin-ciprofloxacin (COL+CIP) and colistin-tobramycin (COL+TOB) combinations were tested by time kill-assays. Each antibiotic alone and in combination at their Cmax values were tested against 4 clinical K. pneumoniae isolates at 1, 2, 4, 6, 8, 12 and 24 h. Effect of colistin and its associations were also assessed at 30 min. Bactericidal activity was defined as ≥3log10 CFU mL-1 decrease compared with initial inoculum. Synergy was defined as ≥2log10CFU mL-1 decrease by the combination compared with the most active single agent. Presence of blaOXA-48, blaNDM, blaVIM, blaIMP, blaKPC and blaCTX-M-1 genes was screened by PCR using specific primers.The blaOXA-48 gene was identified together with blaCTXM-1 group gene in all isolates. COL+MER demonstrated to be synergistic and bactericidal. MER+TOB showed synergistic and bactericidal effect on two strains although, regrowth was seen on other two strains at 24 h. MER+CIP exhibited indifferent effect on the strains.Combination therapy could be a potential alternative to treat MDR K. pneumoniae infections. This combination might prevent resistance development and secondary effects of colistin monotherapy. MER+TOB and MER+CIP might have an isolate-dependent effect, that may not always result in synergism.


Asunto(s)
Infecciones por Klebsiella , Klebsiella pneumoniae , Humanos , Colistina/farmacología , Meropenem/farmacología , Antibacterianos/farmacología , beta-Lactamasas/genética , Proteínas Bacterianas/genética , Ciprofloxacina/farmacología , Tobramicina/farmacología , Pruebas de Sensibilidad Microbiana , Infecciones por Klebsiella/tratamiento farmacológico , Sinergismo Farmacológico
6.
Clin Lab ; 68(6)2022 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-35704730

RESUMEN

BACKGROUND: The purpose of this study is to evaluate the prognostic roles of hemostatic tests including prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer, and antithrombin III in the progression of disease, monitorization of severe, mild and moderate cases, and also to show their relationship with inflammatory markers including C-reactive protein (CRP), procalcitonin, and interleukin-6 (IL-6). METHODS: The study comprised 604 patients (360 men and 244 women) with confirmed SARS-CoV-2 infection admitted to Emergency Department of Istanbul Faculty of Medicine between March 15 and April 15, 2020. The variations in the concentration of coagulation tests and inflammatory markers were observed from the admission to hospital to the 10th day with three-day periods. RESULTS: PT level and PT activity of severe cases were significantly different compared to mild cases (p = 0.012, p = 0.010, respectively). Similarly, aPTT and D-dimer levels in severe cases were significantly higher compared to the mild cases. However, fibrinogen levels of mild cases were significantly lower compared to either moderate or severe cases (p < 0.001, for both). The PT, PT activity, aPTT, and D-Dimer levels in severe cases were significantly different compared with the mild cases. However, fibrinogen level was the highest in severe cases, and higher than either mild or moderate cases. CONCLUSIONS: Our findings reveal the vital importance of measuring coagulation parameters at the time of admission and monitoring them at regular intervals in clinical monitoring of COVID-19 patients, in determining the severity of the disease in terms of the patient's prognosis, and in choosing and applying the appropriate treatment at the right time.


Asunto(s)
COVID-19 , Biomarcadores , COVID-19/diagnóstico , Femenino , Productos de Degradación de Fibrina-Fibrinógeno , Fibrinógeno/análisis , Humanos , Masculino , Tiempo de Tromboplastina Parcial , Pronóstico , Tiempo de Protrombina , SARS-CoV-2
7.
Clin Lab ; 67(7)2021 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-34258985

RESUMEN

BACKGROUND: Early and accurate detection of carbapenemase-producing Enterobacterales (CPE) is fundamental to prevent their spread in hospital environment. Our objective was to compare between four commonly used phenotypic assays and Check-Direct CPE (CDCPE) multiplex PCR in CPE detection. We examined stool samples or rectal swabs for CPE, samples collected from 23 Jan 2017 to 23 Jul 2017 from patients in intensive-care units (ICUs) of our hospital. METHODS: A panel of 98 non-repetitive Enterobacterales isolates with reduced susceptibility to carbapenems were analyzed by means of (i) Modified Hodge Test (MHT), (ii) Blue Carba test (BCT), (iii) Combined Disc Test (CDT), and (iv) The Carbapenem Inactivation Method (CIM). All these phenotypic tests compared with CDCPE. Confirmation and validation of results was achieved by classical PCR and sequencing. RESULTS: Of the 98 non-repetitive Enterobacterales isolates, ninety-one were K. pneumoniae (93%), three K. oxytoca (3%), three E. cloacae (3%) and one E. coli (1%). By classic PCR the carbapenem resistance genes in K. pneumoniae isolates distributed as the followings; 49 blaOXA-48, 34 both blaOXA-48 and blaNDM-1, seven blaNDM-1 and one blaKPC. K. oxytoca; two blaOXA-48, one blaNDM-1. E. cloacae; two blaOXA-48, one blaNDM-1. E. coli; one isolate with both blaOXA-48 and blaNDM-1. The most common carbapenemase gene detected was blaOXA-48 rate of 54% (n = 53) followed by a combination of both blaOXA-48 and blaNDM-1 with rate of 36% (n = 35), only blaNDM-1 9% (n = 9) and blaKPC 1% (n = 1). Among phenotypic tests, we found CIM, MHT, and BCT correctly identified carbapenemase producers with sensitivity of 100%, 98%, and 90.8%, respectively. CONCLUSIONS: Rapid and accurate detection of CRE can be achieved by combination of both phenotypic and molecular tests. Surveillance studies are important both in terms of epidemiology and regulation of the treatment of patients.


Asunto(s)
Antibacterianos , Escherichia coli , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Proteínas Bacterianas , Humanos , Pruebas de Sensibilidad Microbiana , beta-Lactamasas/genética
8.
Int J Infect Dis ; 105: 756-762, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33737128

RESUMEN

OBJECTIVES: Disease severity, previous medications and immunosuppressive agents could affect the antibody response against SARS-CoV-2. This study aimed to analyze variables affecting the humoral response to SARS-CoV-2. METHODS: This prospective cohort study included adult patients who recovered from COVID-19 and were admitted to a COVID-19 follow-up unit. Eight patient groups were defined in accordance with the results of thoracic computed tomography (CT), SARS-CoV-2 PCR test, and tocilizumab or anakinra use during active disease. Anti-S IgG antibodies were determined by ELISA in serum samples. Anti-S positive and negative cases were compared. RESULTS: A total of 518 patients were included in the study. SARS-CoV-2 IgG antibodies were positive in 82.8% of patients. SARS-CoV-2 PCR positivity, extent of lung involvement on CT, and time to antibody testing were independently associated with antibody positivity. Tocilizumab, anakinra or prednisolone use was not a factor affecting the antibody response. The rate of antibody response and sample/CO values among antibody-positive patients showed a linear relationship with the extent of lung involvement on CT. CONCLUSIONS: The use of tocilizumab, anakinra and prednisolone for COVID-19 did not affect the antibody response against SARS-CoV-2. The main driver of antibody response among patients with COVID-19 was the extent of pulmonary involvement on CT.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Antivirales/sangre , Tratamiento Farmacológico de COVID-19 , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Prednisolona/uso terapéutico , SARS-CoV-2/inmunología , Anticuerpos Antivirales/inmunología , Estudios de Cohortes , Quimioterapia Combinada , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X
9.
J Clin Lab Anal ; 34(12): e23541, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33025699

RESUMEN

BACKGROUND: The aim of this study was to provide information about the spread and characteristics of the vancomycin-resistant Enterococcus faecium isolates (VREfm) in Turkey. METHODS: Seventy-one nonduplicate consecutive isolates of VREfm were obtained from various clinical specimens of inpatients treated at university or training hospitals in seven regions of Turkey. Further characteristics included antibiotic susceptibility testing, pulsed-field gel electrophoresis (PFGE) of SmaI-digested genomic DNA, and multilocus sequence typing (MLST) of selected isolates. The presence of vancomycin resistance and virulence genes (esp and hyl) was investigated by polymerase chain reaction (PCR). RESULTS: All VREfm isolates had MICs to vancomycin of ≥32 mg/L and contained the vanA gene. The presence of esp gene was identified in 64 and hyl in eight VREfm isolates. All VREfm showed the multiresistance phenotype, including ampicillin (99%), penicillin (99%), imipenem (99%), ciprofloxacin (87%), moxifloxacin (87%), erythromycin (97%), streptomycin (86%), gentamicin (82%), tetracycline (70%), and teicoplanin (99%). All were susceptible to tigecycline while quinupristin-dalfopristin (97%) and linezolid (93%) were the most active other agents. Analysis of the PFGE profiles showed that 53 (74.6%) VREfm isolates shared a similar electrophoretic profile, designed as type 1, and were closely related (>85%). The sequence type was identified by MLST in 44 VRE isolates with unrelated or closely related PFGE patterns. MLST revealed that nosocomial spread of VREfm resulted from dissemination of lineage C1 E faecium clones. Sequence types ST78, ST203, and ST117 were the most frequently isolated. This is the first report of ST733 around the world. CONCLUSIONS: Lineage C1 clones are disseminated among clinical VREfm isolates in seven different regions in Turkey. Regarding VREfm isolates, the worldwide epidemic strains are in circulation in Turkey.


Asunto(s)
Infección Hospitalaria , Enterococcus faecium , Infecciones por Bacterias Grampositivas , Enterococos Resistentes a la Vancomicina , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Niño , Preescolar , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , Estudios Transversales , Farmacorresistencia Bacteriana/genética , Electroforesis en Gel de Campo Pulsado , Enterococcus faecium/clasificación , Enterococcus faecium/efectos de los fármacos , Enterococcus faecium/genética , Enterococcus faecium/patogenicidad , Femenino , Infecciones por Bacterias Grampositivas/epidemiología , Infecciones por Bacterias Grampositivas/microbiología , Humanos , Lactante , Masculino , Persona de Mediana Edad , Tipificación de Secuencias Multilocus , Turquía/epidemiología , Enterococos Resistentes a la Vancomicina/clasificación , Enterococos Resistentes a la Vancomicina/efectos de los fármacos , Enterococos Resistentes a la Vancomicina/genética , Enterococos Resistentes a la Vancomicina/patogenicidad , Factores de Virulencia/genética , Adulto Joven
10.
BMC Infect Dis ; 20(1): 788, 2020 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-33096990

RESUMEN

BACKGROUND: Tuberculous meningitis (TBM) represents a diagnostic and management challenge to clinicians. The "Thwaites' system" and "Lancet consensus scoring system" are utilized to differentiate TBM from bacterial meningitis but their utility in subacute and chronic meningitis where TBM is an important consideration is unknown. METHODS: A multicenter retrospective study of adults with subacute and chronic meningitis, defined by symptoms greater than 5 days and less than 30 days for subacute meningitis (SAM) and greater than 30 days for chronic meningitis (CM). The "Thwaites' system" and "Lancet consensus scoring system" scores and the diagnostic accuracy by sensitivity, specificity, and area under the curve of receiver operating curve (AUC-ROC) were calculated. The "Thwaites' system" and "Lancet consensus scoring system" suggest a high probability of TBM with scores ≤4, and with scores of ≥12, respectively. RESULTS: A total of 395 patients were identified; 313 (79.2%) had subacute and 82 (20.8%) with chronic meningitis. Patients with chronic meningitis were more likely caused by tuberculosis and had higher rates of HIV infection (P < 0.001). A total of 162 patients with TBM and 233 patients with non-TBM had unknown (140, 60.1%), fungal (41, 17.6%), viral (29, 12.4%), miscellaneous (16, 6.7%), and bacterial (7, 3.0%) etiologies. TMB patients were older and presented with lower Glasgow coma scores, lower CSF glucose and higher CSF protein (P < 0.001). Both criteria were able to distinguish TBM from bacterial meningitis; only the Lancet score was able to differentiate TBM from fungal, viral, and unknown etiologies even though significant overlap occurred between the etiologies (P < .001). Both criteria showed poor diagnostic accuracy to distinguish TBM from non-TBM etiologies (AUC-ROC was <. 5), but Lancet consensus scoring system was fair in diagnosing TBM (AUC-ROC was .738), sensitivity of 50%, and specificity of 89.3%. CONCLUSION: Both criteria can be helpful in distinguishing TBM from bacterial meningitis, but only the Lancet consensus scoring system can help differentiate TBM from meningitis caused by fungal, viral and unknown etiologies even though significant overlap occurs and the overall diagnostic accuracy of both criteria were either poor or fair.


Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Criptococosis/diagnóstico , Cryptococcus neoformans/inmunología , VIH/genética , Meningitis Fúngica/diagnóstico , Meningitis Viral/diagnóstico , Mycobacterium tuberculosis/genética , Proyectos de Investigación , Tuberculosis Meníngea/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Enfermedad Crónica , Criptococosis/microbiología , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Meningitis Fúngica/líquido cefalorraquídeo , Meningitis Fúngica/microbiología , Meningitis Viral/líquido cefalorraquídeo , Meningitis Viral/virología , Persona de Mediana Edad , Mycobacterium tuberculosis/aislamiento & purificación , Estudios Retrospectivos , Sensibilidad y Especificidad , Tuberculosis Meníngea/líquido cefalorraquídeo , Tuberculosis Meníngea/microbiología , Adulto Joven
11.
Antimicrob Resist Infect Control ; 9(1): 70, 2020 05 19.
Artículo en Inglés | MEDLINE | ID: mdl-32430058

RESUMEN

BACKGROUND: Treatment of pandrug-resistant isolates often necessitates combination therapy. Checkerboard synergy and time-killing assay tests were performed to evaluate the benefits of a triple combination with meropenem, ertapenem, and colistin against 10 colistin-resistant K. pneumoniae clinical isolates harboring different ß-lactamases. (blaOXA-48, blaNDM). MATERIALS AND METHODS: In this study, ertapenem and meropenem (ERT/MEM), meropenem and colistin (MEM/COL), ertapenem, meropenem and colistin (ERT/MEM/COL) combinations were tested using checkerboard techniques and time-kill assays of each antibiotic alone and in combination against 10 colistin-resistant clinical K. pneumoniae isolates. An analysis of K. pneumoniae isolate B6 using a scanning electron microscope revealed morphologic changes in the cell surface after treatment with each antibiotic both alone and in combination. The whole genome of K. pneumoniae KPNB1 was sequenced using an Ion Torrent PGM sequencer. RESULTS: According to the checkboard results, synergistic combinations were observed with ertapenem/meropenem (5/10 isolates), meropenem/colistin (7/10) and ertapenem/meropenem/colistin (9/10); no antagonism was observed for all combinations. For the time-kill assay results; synergism and bactericidal effects were observed with meropenem/colistin (10/10) and with ertapenem/meropenem/colistin (10/10) combinations, and an indifference effect was observed with the ertapenem and meropenem (10/10) combination. Strain number 1 was found 100% identical to Klebsiella pneumoniae subsp. pneumoniae HS11286 according to the outcomes of complete genome sequence analysis, and the strain carried the genes blaOXA-181, blaCTXM-15, blaNDM, arr-3, aac (6')-Ib-cr, rmtF, and catB1. CONCLUSION: Using double carbapenem antibiotics with colistin could be a potential alternative to treat colistin and carbapenem-resistant K. pneumoniae. The present study is the first Turkish report of OXA-181-type carbapenemase causing colistin resistance.


Asunto(s)
Carbapenémicos/farmacología , Colistina/farmacología , Klebsiella pneumoniae/clasificación , Secuenciación Completa del Genoma/métodos , Sinergismo Farmacológico , Genoma Bacteriano , Secuenciación de Nucleótidos de Alto Rendimiento , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/aislamiento & purificación , Microscopía Electrónica de Rastreo , Filogenia , beta-Lactamasas/metabolismo
12.
Tohoku J Exp Med ; 247(3): 189-195, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30890665

RESUMEN

Encephalitis is an inflammatory process involving the brain parenchyma associated with neurologic dysfunction. The main causes of infectious encephalitis are viruses, including Herpes simplex virus type 1 (HSV-1). As the mortality rate of HSV-1 encephalitis could be reduced with early acyclovir treatment, it is imperative to distinguish HSV-1 encephalitis from other type of viral encephalitis as early as possible. However, sophisticated methods for definitive diagnosis of HSV-1 encephalitis are not readily available. We aimed to explore distinctive clinical and laboratory features of HSV-1 encephalitis. All of the adult patients with viral encephalitis hospitalized between 2011-2017 were enrolled, including 16 patients with HSV-1 encephalitis and 51 patients non-HSV-1 viral encephalitis. Determination of viruses in cerebrospinal fluid was performed by PCR tests. Female sex, hyponatremia, and abnormalities in MRI were independently associated with HSV-1 encephalitis (p < 0.05 for each). In particular, hyponatremia (< 135 mEq/L) was found in nine patients with HSV-1 encephalitis (56.3%) and 10 patients with non-HSV-1 viral encephalitis (19.6%) (p = 0.005). As serum sodium is determined easily and quickly in clinical practice, the presence of hyponatremia among patients with viral encephalitis could be helpful for the early diagnosis of HSV-1 encephalitis before cerebrospinal fluid PCR results were available. Moreover, the presence of positive finding in MRI could further support the diagnosis. This is the first study that compared the serum sodium levels among patients between HSV-1 and non-HSV-1 viral encephalitis. We thus propose the diagnostic value of hyponatremia for HSV-1 encephalitis.


Asunto(s)
Encefalitis por Herpes Simple/complicaciones , Encefalitis por Herpes Simple/virología , Encefalitis Viral/complicaciones , Encefalitis Viral/virología , Herpesvirus Humano 1/fisiología , Hiponatremia/complicaciones , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/virología , Encefalitis por Herpes Simple/epidemiología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Resultado del Tratamiento
13.
Microb Drug Resist ; 25(4): 551-557, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30457928

RESUMEN

Background: Fifty isolates of Klebsiella pneumoniae isolated from clinical samples between 2012 and 2016 that were found to be resistant to carbapenems were included in this study. Materials and Methods: Resistance genes were investigated by performing PCR. Plasmid typing was performed using PCR-based replicon typing. The clonal relationships between the strains were investigated using pulsed-field gel electrophoresis (PFGE). Results: OXA-48-type carbapenemase genes were detected in 86% (n = 43/50) of K. pneumoniae isolates, whereas NDM-type carbapenemase genes were detected in 14% (n = 7/50) of the isolates. blaTEM was detected 60% (n = 30) of the strains, blaSHV in 78% (n = 39), blaCTX-M-1 in 48% (n = 24), and blaCTX-M-2-type ß-lactamase in 10% (n = 5). blaCTX-M-1 and blaSHV were concomitantly distributed in 40% (n = 20) of the strains, blaTEM and blaSHV in 54% (n = 27), blaTEM, blaSHV, and blaCTX-M-1 in 32% (n = 16) and blaCTX-M-1 and blaCTX-M-2 in 10% (n = 5). Strain numbers 66, 69, 76, 77, and 78 coproduced carbapenemases, blaCTX-M-1 and blaCTX-M-2 in addition to blaOXA-48 or blaNDM-1 that were described as hybrid strains. IncR-type replicon was found in 50% (n = 25) of 50 isolates with plasmid typing, whereas IncA/C-type replicon was detected in 40% (n = 20) and IncFIIK-type replicon in 18% (n = 9) of the isolates. Outcomes of the transformation experiments showed that the OXA-48 gene was carried to the receiver cell on FII plasmids. No dominant epidemic clone was detected through PFGE. Conclusion: OXA-48 carbapenemase was found to be the most prevalent type of enzyme in our hospital, and the presence of NDM-1-type carbapenemase-carrying strain and an increase in their rate were detected.


Asunto(s)
Antibacterianos/farmacología , Carbapenémicos/farmacología , Farmacorresistencia Bacteriana/genética , Klebsiella pneumoniae/genética , Replicón/genética , Proteínas Bacterianas/genética , Humanos , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/microbiología , Pruebas de Sensibilidad Microbiana/métodos , Tipificación de Secuencias Multilocus/métodos , Plásmidos/genética , Reacción en Cadena de la Polimerasa/métodos , beta-Lactamasas/genética
14.
Int J Infect Dis ; 70: 10-14, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29476898

RESUMEN

OBJECTIVES: We described the clinical outcomes of the diabetic patients who had foot infections with multidrug resistant organisms. METHODS: We included the patients with diabetic foot infections (DFI) from 19 centers, between May 2011 and December 2015. Infection was defined according to IDSA DFI guidelines. Patients with severe infection, complicated moderate infection were hospitalized. The patients were followed-up for 6 months after discharge. RESULTS: In total, 791 patients with DFI were included, 531(67%) were male, median age was 62 (19-90). Severe infection was diagnosed in 85 (11%) patients. Osteomyelitis was diagnosed in 291(36.8%) patients. 536 microorganisms were isolated, the most common microorganisms were S. aureus (20%), P. aeruginosa (19%) and E. coli (12%). Methicillin resistance (MR) rate among Staphylococcus aureus isolates was 31%. Multidrug resistant bacteria were detected in 21% of P. aeruginosa isolates. ESBL (+) Gram negative bacteria (GNB) was detected in 38% of E. coli and Klebsiella isolates. Sixty three patients (8%) were re-hospitalized. Of the 791 patiens, 127 (16%) had major amputation, and 24 (3%) patients died. In multivariate analysis, significant predictors for fatality were; dialysis (OR: 8.3, CI: 1.82-38.15, p=0.006), isolation of Klebsiella spp. (OR:7.7, CI: 1.24-47.96, p=0.028), and chronic heart failure (OR: 3, CI: 1.01-9.04, p=0.05). MR Staphylococcus was detected in 21% of the rehospitalized patients, as the most common microorganism (p<0.001). CONCLUSION: Among rehospitalized patients, methicillin resistant Staphylococcus infections was detected as the most common agent, and Klebsiella spp. infections were found to be significantly associated with fatality.


Asunto(s)
Amputación Quirúrgica/estadística & datos numéricos , Pie Diabético/microbiología , Resistencia a Múltiples Medicamentos/fisiología , Osteomielitis/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Pie Diabético/tratamiento farmacológico , Pie Diabético/fisiopatología , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Femenino , Humanos , Klebsiella pneumoniae/efectos de los fármacos , Masculino , Persona de Mediana Edad , Osteomielitis/tratamiento farmacológico , Osteomielitis/fisiopatología , Evaluación del Resultado de la Atención al Paciente , Readmisión del Paciente/estadística & datos numéricos , Pseudomonas aeruginosa/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos
15.
Clin Lab ; 63(3): 515-522, 2017 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-28271693

RESUMEN

BACKGROUND: Rapid, simple, and accurate laboratory detection of carbapenemases is very important for proper antibiotic therapy and infection control. METHODS: In this study, carbapenem-nonsusceptible Enterobacteriaceae (CRE) isolates were used to evaluate the performance of a new lateral flow immunochromatographic (IC) assay, the OXA-48 and KPC K-SeT assay, and modified Blue-Carba test (BCT) for the rapid detection of OXA-48 carbapenemase in comparison with polymerase chain reaction (PCR) amplification. These CREs of various enterobacterial species were isolated from various clinical samples including OXA-48 (47), NDM-1 (6), KPC-1 (1), IMP-1 (1), VIM-2,-4 (2), IMP-2 (1), OXA-51 (1), and OXA-23 (1) producers. RESULTS: The OXA-48 K-SeT test detected all OXA-48 carbapenemase producers with 100% sensitivity and specificity. The BCT detected carbapenemase producers with 93% sensitivity and 100% specificity. CONCLUSIONS: Both IC assays and BCT tests have good performance and are easy to perform, rapid, simple to interpret, and highly sensitive. We suggest that BCT can be used initially as an accurate, inexpensive, and rapid phenotypic confirmation test to identify Class A, B, and D carbapenemases in the routine diagnostic microbiology laboratory, thus allowing the detection of carbapenemase activity directly from bacterial cultures.


Asunto(s)
Reacción en Cadena de la Polimerasa , Proteínas Bacterianas , Carbapenémicos , Cromatografía de Afinidad , Enterobacteriaceae , Humanos , beta-Lactamasas
17.
Neurol India ; 64(5): 896-905, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27625226

RESUMEN

AIMS: There is no report on the factors affecting the resolution of symptoms related to meningitis during treatment of tuberculous meningitis (TBM). Thus, we examined the factors associated with early therapeutic responses. MATERIALS AND METHODS: This multicenter study included 507 patients with microbiologically confirmed TBM. However, 94 patients eligible for the analysis were included in this study from 24 centers. Six out of 94 patients died and the statistical analysis was performed with 88 survivors. Early and late responder groups were compared in the statistical analysis. P < 0.05 were considered to show a significant difference. RESULTS: In the multivariate analysis, the presence of vasculitis (P = 0.029, OR = 10.491 [95% CI, 1.27-86.83]) was found to be significantly associated with a delayed fever response whereas hydrocephalus was associated with altered mental status for >9 days duration (P = 0.005, OR = 5.740 [95% CI, 1.68-19.57]). According to linear regression analysis, fever was significantly persisting (>7 days) in the presence of vasculitis (17.5 vs. 7, P< 0.001) and hydrocephalus (11 vs. 7, P = 0.029). Hydrocephalus was significantly associated with persisting headache (21 vs. 12, P = 0.025), delayed recovery of consciousness (19.5 vs. 7, P = 0.001), and a delay in complete recovery (21 vs. 14, P = 0.007) in the linear regression analysis. Following institution of treatment, the complaints seemed to disappear in up to 2 weeks among TBM survivors. CONCLUSIONS: In the absence of hydrocephalus or vasculitis, one week of anti-tuberculosis treatment seems to be adequate for the resolution of TBM symptoms. Hydrocephalus and vasculitis delay the resolution of TBM symptoms in response to antimycobacterial treatment.


Asunto(s)
Antituberculosos/uso terapéutico , Hidrocefalia/complicaciones , Tuberculosis Meníngea/tratamiento farmacológico , Vasculitis/complicaciones , Humanos , Pronóstico , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Tuberculosis Meníngea/complicaciones
18.
Ann Clin Microbiol Antimicrob ; 14: 47, 2015 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-26538030

RESUMEN

BACKGROUND: Tuberculous meningitis (TBM) caused by Mycobacterium tuberculosis resistant to antituberculosis drugs is an increasingly common clinical problem. This study aimed to evaluate drug resistance profiles of TBM isolates in adult patients in nine European countries involving 32 centers to provide insight into the empiric treatment of TBM. METHODS: Mycobacterium tuberculosis was cultured from the cerebrospinal fluid (CSF) of 142 patients and was tested for susceptibility to first-line antituberculosis drugs, streptomycin (SM), isoniazid (INH), rifampicin (RIF) and ethambutol (EMB). RESULTS: Twenty of 142 isolates (14.1 %) were resistant to at least one antituberculosis drug, and five (3.5 %) were resistant to at least INH and RIF, [multidrug resistant (MDR)]. The resistance rate was 12, 4.9, 4.2 and 3.5 % for INH, SM, EMB and RIF, respectively. The monoresistance rate was 6.3, 1.4 and 0.7 % for INH, SM and EMB respectively. There was no monoresistance to RIF. The mortality rate was 23.8 % in fully susceptible cases while it was 33.3 % for those exhibiting monoresistance to INH, and 40 % in cases with MDR-TBM. In compared to patients without resistance to any first-line drug, the relative risk of death for INH-monoresistance and MDR-TBM was 1.60 (95 % CI, 0.38-6.82) and 2.14 (95 % CI, 0:34-13:42), respectively. CONCLUSION: INH-resistance and MDR rates seemed not to be worrisome in our study. However, considering their adverse effects on treatment, rapid detection of resistance to at least INH and RIF would be most beneficial for designing anti-TB therapy. Still, empiric TBM treatment should be started immediately without waiting the drug susceptibility testing.


Asunto(s)
Antituberculosos/farmacología , Farmacorresistencia Bacteriana , Mycobacterium tuberculosis/efectos de los fármacos , Tuberculosis Meníngea/microbiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Líquido Cefalorraquídeo/microbiología , Europa (Continente)/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/aislamiento & purificación , Prevalencia , Estudios Retrospectivos , Análisis de Supervivencia , Tuberculosis Meníngea/epidemiología , Tuberculosis Meníngea/mortalidad , Adulto Joven
19.
Clin Lab ; 61(8): 941-50, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26427137

RESUMEN

BACKGROUND: The aim of this study is to detect the presence of and possible relation between virulence genes and antibiotic resistance in E. coli strains isolated from patients with acute, uncomplicated urinary tract infections (UTI). METHODS: 62 E. coli strains isolated from patients with acute, uncomplicated urinary tract infections (50 strains isolated from acute uncomplicated cystitis cases (AUC); 12 strains from acute uncomplicated pyelonephritis cases (AUP)) were screened for virulence genes [pap (pyelonephritis-associated pili), sfa/foc (S and F1C fimbriae), afa (afimbrial adhesins), hly (hemolysin), cnf1 (cytotoxic necrotizing factor), aer (aerobactin), PAI (pathogenicity island marker), iroN (catecholate siderophore receptor), ompT (outer membrane protein T), usp (uropathogenic specific protein)] by PCR and for antimicrobial resistance by disk diffusion method according to CLSI criteria. RESULTS: It was found that 56 strains (90.3%) carried at least one virulence gene. The most common virulence genes were ompT (79%), aer (51.6%), PAI (51.6%) and usp (56.5%). 60% of the strains were resistant to at least one antibiotic. The highest resistance rates were against ampicillin (79%) and co-trimoxazole (41.9%). Fifty percent of the E. coli strains (31 strains) were found to be multiple resistant. Eight (12.9%) out of 62 strains were found to be ESBL positive. Statistically significant relationships were found between the absence of usp and AMP - SXT resistance, iroN and OFX - CIP resistance, PAI and SXT resistance, cnf1 and AMP resistance, and a significant relationship was also found between the presence of the afa and OFX resistance. CONCLUSIONS: No difference between E. coli strains isolated from two different clinical presentations was found in terms of virulence genes and antibiotic susceptibility.


Asunto(s)
Antibacterianos/uso terapéutico , Proteínas Bacterianas/genética , Farmacorresistencia Bacteriana Múltiple/genética , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología , Factores de Virulencia/genética , Enfermedad Aguda , Escherichia coli/clasificación , Escherichia coli/aislamiento & purificación , Escherichia coli/patogenicidad , Infecciones por Escherichia coli/diagnóstico , Infecciones por Escherichia coli/orina , Humanos , Pruebas de Sensibilidad Microbiana , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/orina , Orina/microbiología , Virulencia
20.
Mikrobiyol Bul ; 49(3): 461-6, 2015 Jul.
Artículo en Turco | MEDLINE | ID: mdl-26313288

RESUMEN

BCG (Bacillus Calmette-Guérin) vaccine is a widely used vaccine with the recommendation of World Health Organization to protect children against miliary tuberculosis (TB) and TB meningitis. Severe side effects related to this vaccine mostly manifest in the presence of underlying immunosuppressive disease. In this report, an infant case with unknown chronic granulomatous disease (CGD) who developed disseminated BCG infection after administration of BCG vaccine, was presented. High fever, left axillary lymphadenopathy and hepatosplenomegaly have developed in a 3-month 28-day female infant, without a known health problem, following BCG vaccination. The acid-fast bacilli (ARB) was isolated from the material of excised lymph node cultivated in Löwenstein-Jensen medium, and the isolate was identified as Mycobacterium bovis. Mycobacterium tuberculosis complex DNA was detected in the axillary lymph node sample by polymerase chain reaction. Anti-tuberculous treatment included 20 mg/kg of rifampicin+10 mg/kg of isoniazid+15 mg/kg of ethambutol+30 mg/kg of streptomycin was started. The patient was then further evaluated for immunodeficiency and on the basis of the results of dihydroamine and LAD (lymphocyte adhesion defect) tests, diagnosed as autosomal recessive CGD. Based on the anamnesis, there was no known immunodeficiency history both in the case during neonatal period and her family members. Interferon-gamma therapy, which is recommended for the patients with CGD living in endemic areas, was initiated. Our patient's fever dropped at the 15th day of anti-tuberculosis treatment, and she was discharged on the 35th day and continued to receive treatment at home. The patient was followed up at outpatient clinic and had no additional complaints; her hepatosplenomegaly was back to normal at the third month. As a result, since BCG vaccine is contraindicated in CGD carriers, newborns with a family history of CGD should be immunologically examined and BCG vaccine should be avoided until the results are obtained. In addition, newborns without a family history, diagnosed as disseminated mycobacterial infection following BCG vaccination, should be evaluated for an underlying immunodeficiency condition.

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